tbuckley/cabot-search huggingface dataset:
Hyperhomocysteinemia potentiates megakaryocyte differentiation and thrombopoiesis via GH-PI3K-Akt axis
Authors: Wenjing Lei, Zhuoliang Liu, Zhiyuan Su, Panpan Meng, Chun Zhou, Xiaomei Chen, Zheng Hu, An Xiao, Miaomiao Zhou, Liping Huang, Yiyue Zhang, Xianhui Qin, Junping Wang, Fengxin Zhu, Jing Nie
Journal: Journal of Hematology & Oncology (2023)

Abstract Hyperhomocysteinemia (HHcy) is closely associated with thrombotic diseases such as myocardial infarction and stroke. Enhanced platelet activation was observed in animals and humans with HHcy. However, the influence of HHcy on thrombopoiesis remains largely unknown. Here, we reported increased platelet count (PLT) in mice and zebrafish with HHcy. In hypertensive patients (n = 11,189), higher serum level of total Hcy was observed in participants with PLT ≥ 291 × 10 9 /L (full adjusted β, 0.59; 95% CI 0.14, 1.04). We used single-cell RNA sequencing (scRNA-seq) to characterize the impact of Hcy on transcriptome, cellular heterogeneity, and developmental trajectories of megakaryopoiesis from human umbilical cord blood (hUCB) CD34 + cells. Together with in vitro and in vivo analysis, we demonstrated that Hcy promoted megakaryocytes (MKs) differentiation via growth hormone (GH)-PI3K-Akt axis. Moreover, the effect of Hcy on thrombopoiesis is independent of thrombopoietin (TPO) because administration of Hcy also led to a significant increase of PLT in homozygous TPO receptor ( Mpl ) mutant mice and zebrafish. Administration of melatonin effectively reversed Hcy-induced thrombopoiesis in mice. ScRNA-seq showed that melatonin abolished Hcy-facilitated MK differentiation and maturation, inhibited the activation of GH-PI3K-Akt signaling. Our work reveals a previously unrecognized role of HHcy in thrombopoiesis and provides new insight into the mechanisms by which HHcy confers an increased thrombotic risk. Trial Registration clinicaltrials.gov Identifier: NCT00794885.
Atogepant for the preventive treatment of chronic migraine (PROGRESS): a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Patricia Pozo-Rosich, Jessica Ailani, Messoud Ashina, Peter J Goadsby, Richard B Lipton, Uwe Reuter, Hua Guo, Brittany Schwefel, Kaifeng Lu, Ramesh Boinpally, Rosa Miceli, Rosa De Abreu Ferreira, Emily McCusker, Sung Yun Yu, Lawrence Severt, Michelle Finnegan, Joel M Trugman
Journal: The Lancet (2023)
Searching for answers: expert pattern recognition and planning
Authors: Fernand Gobet, Andrew J. Waters
Journal: Trends in Cognitive Sciences (2023)

Does expertise mostly stem from pattern recognition or look-ahead search? van Opheusden et al. contribute to this important debate in cognitive psychology and artificial intelligence (AI) with a multi-method, multi-experiment study and a new model. Using a novel, relatively simple board game, they show that players increase depth of search when improving their skill.
Deletion of protein tyrosine phosphatase SHP-1 restores SUMOylation of podocin and reverses the progression of diabetic kidney disease
Authors: Farah Lizotte, Marina Rousseau, Benoit Denhez, Dominique Lévesque, Andréanne Guay, HongBo Liu, Julie Moreau, Sarah Higgins, Robert Sabbagh, Katalin Susztak, François-Michel Boisvert, Anne Marie Côté, Pedro Geraldes
Journal: Kidney International (2023)

Both clinical and experimental data suggest that podocyte injury is involved in the onset and progression of diabetic kidney disease (DKD). Although the mechanisms underlying the development of podocyte loss are not completely understood, critical structural proteins such as podocin play a major role in podocyte survival and function. We have reported that the protein tyrosine phosphatase SHP-1 expression increased in podocytes of diabetic mice and glomeruli of patients with diabetes. However, the in vivo contribution of SHP-1 in podocytes is unknown. Conditional podocyte-specific SHP-1-deficient mice (Podo-SHP-1-/-) were generated to evaluate the impact of SHP-1 deletion at four weeks of age (early) prior to the onset of diabetes and after 20 weeks (late) of diabetes (DM; Ins2+/C96Y) on kidney function (albuminuria and glomerular filtration rate) and kidney pathology. Ablation of the SHP-1 gene specifically in podocytes prevented and even reversed the elevated albumin/creatinine ratio, glomerular filtration rate progression, mesangial cell expansion, glomerular hypertrophy, glomerular basement membrane thickening and podocyte foot process effacement induced by diabetes. Moreover, podocyte-specific deletion of SHP-1 at an early and late stage prevented diabetes-induced expression of collagen IV, fibronectin, transforming growth factor-β, transforming protein RhoA, and serine/threonine kinase ROCK1, whereas it restored nephrin, podocin and cation channel TRPC6 expression. Mass spectrometry analysis revealed that SHP-1 reduced SUMO2 post-translational modification of podocin while podocyte-specific deletion of SHP-1 preserved slit diaphragm protein complexes in the diabetic context. Thus, our data uncovered a new role of SHP-1 in the regulation of cytoskeleton dynamics and slit diaphragm protein expression/stability, and its inhibition preserved podocyte function preventing DKD progression.
The potential of saliva as an accessible and sensitive sample type for the detection of respiratory pathogens and host immunity
Authors: Claire S Laxton, Chikondi Peno, Anne M Hahn, Orchid M Allicock, Stephanie Perniciaro, Anne L Wyllie
Journal: The Lancet Microbe (2023)

Despite its prominence in early scientific records, the usefulness of saliva as a respiratory specimen has been de-emphasised over the past century. However, due to its low cost and reliance on specific supply chains and the non-invasive nature of its collection, its benefits over swab-based specimens are again becoming increasingly recognised. These benefits were highlighted over the course of the COVID-19 pandemic, where saliva emerged as a more practical, clinically non-inferior sample type for the detection of SARS-CoV-2 and saw numerous saliva-based diagnostic tests approved for clinical use. Looking forward, as saliva uniquely contains both respiratory secretions and immunological components, it has potentially wide applications, ranging from clinical diagnostics to post-vaccine disease burden and immunity surveillance. This Personal View seeks to summarise the existing evidence for the use of saliva in detecting respiratory pathogens, beyond SARS-CoV-2, as well as detailing methodological factors that can influence sample quality and thus, clinical utility.
Validation of agent-based models of surface receptor oligomerisation
Authors: Joanne C. Clark, Steve P. Watson, Dylan M. Owen
Journal: Trends in Pharmacological Sciences (2023)

Receptor dimerisation and higher order oligomerisation regulates signalling by a wide variety of transmembrane receptors. We discuss how agent-based modelling (ABM) combined with advanced microscopy and structural studies can provide new insights into the regulation of clustering, including spatial considerations, revealing novel targets for therapeutic intervention.
A Novel Patient‐Personalized Nanovector Based on Homotypic Recognition and Magnetic Hyperthermia for an Efficient Treatment of Glioblastoma Multiforme (Adv. Healthcare Mater. 19/2023)
Authors: Daniele De Pasquale, Carlotta Pucci, Andrea Desii, Attilio Marino, Doriana Debellis, Luca Leoncino, Mirko Prato, Stefania Moscato, Simone Amadio, Pietro Fiaschi, Alessandro Prior, Gianni Ciofani
Journal: Advanced Healthcare Materials (2023)

Personalized Medicine In article 2203120 by Daniele De Pasquale, Carlotta Pucci, Gianni Ciofani, and co-workers, patient-derived cancer cell membrane-coated magnetic/lipid nanovectors allow for a precise and personalized targeting against glioblastoma multiforme cells. The combination of magnetic hyperthermia and chemotherapy, the latter selected based on patients' response, improve antitumor efficacy, providing an innovative and promising therapeutic tool to treat brain cancer.
Comparative analysis of immune-related adverse events among patients with melanoma on immune checkpoint inhibitors: a retrospective cohort study
Authors: Catherina X Pan, Daniel Y Kim, Charles B Lau, William C Lau, Rachael Rowley, Ruhi Kanwar, Nicole R LeBoeuf, Vinod E Nambudiri
Journal: British Journal of Dermatology (2023)

In a large, multi-institutional cohort of 672 patients with melanoma, we examined the comparative incidence and severity of immune-related adverse events among patients receiving first-line immune checkpoint inhibitors. Comparing PD-1 inhibitors, nivolumab was associated with significantly lower risk of high-grade toxicity onset compared with pembrolizumab on unadjusted logistic regression analysis. Compared with pembrolizumab, use of the CTLA-4 inhibitor ipilimumab was associated with a significant increase in risk of gastrointestinal, but not endocrine and cutaneous toxicities.
Updated Overall Survival by Circulating Tumor DNA Status from the Phase 3 IMvigor010 Trial: Adjuvant Atezolizumab Versus Observation in Muscle-invasive Urothelial Carcinoma
Authors: Thomas Powles, Zoe June Assaf, Viraj Degaonkar, Petros Grivas, Maha Hussain, Stephane Oudard, Jürgen E. Gschwend, Peter Albers, Daniel Castellano, Hiroyuki Nishiyama, Siamak Daneshmand, Shruti Sharma, Himanshu Sethi, Alexey Aleshin, Yi Shi, Nicole Davarpanah, Corey Carter, Joaquim Bellmunt, Sanjeev Mariathasan
Journal: European Urology (2023)
Hematoma-like dynamic hydrogelation through natural glycopeptide molecular recognition for infected bone fracture repair
Authors: Shenghao Wang, Wenbo He, Huan Wang, Dachuan Liu, Miao Wang, Huilin Yang, Guoqing Pan, Bin Li
Journal: Bioactive Materials (2023)

Infected bone fractures remain a major clinical challenge for orthopedic surgeons. From a tissue regeneration perspective, biomaterial scaffolds with antibacterial and osteoinductive activities are highly desired, while advanced materials capable of mimicking the pathological microenvironment during the healing process of infected tissues remain an area deserving more research. Hematoma, the gel-like blood coagulum, plays an essential role in bone fracture repair because of its ability to serve as a dynamic and temporary scaffold with cytokines for both pathogen elimination and tissue healing. In light of this, we designed a dynamic hydrogel with hematoma-like antimicrobial or reparative performance for infected bone fracture repair in this study. The proposed dynamic hydrogel network was based on the reversible recognition of a natural glycopeptide antibiotic vancomycin (Van) and its target dipeptide D-Ala-D-Ala (AA), which could serve as a hematoma-like scaffold for obliterating bacteria in the fracture region and promoting bone repair by introducing an endogenous osteogenic peptide (OGP). In vivo experiments demonstrated that the hydrogel could rapidly eradicate bacteria, improve bone regeneration and restore the local inflammatory microenvironment. Together, findings from this study imply that the use of hematoma-like dynamic hydrogel could lead to a biomimetic revolution in surgical strategies against susceptible bone fractures.
Optical coherence tomography angiography in diabetic retinopathy
Authors: Nadia K. Waheed, Richard B. Rosen, Yali Jia, Marion R. Munk, David Huang, Amani Fawzi, Victor Chong, Quan Dong Nguyen, Yasir Sepah, Elizabeth Pearce
Journal: Progress in Retinal and Eye Research (2023)

There remain many unanswered questions on how to assess and treat the pathology and complications that arise from diabetic retinopathy (DR). Optical coherence tomography angiography (OCTA) is a novel and non-invasive three-dimensional imaging method that can visualize capillaries in all retinal layers. Numerous studies have confirmed that OCTA can identify early evidence of microvascular changes and provide quantitative assessment of the extent of diseases such as DR and its complications. A number of informative OCTA metrics could be used to assess DR in clinical trials, including measurements of the foveal avascular zone (FAZ; area, acircularity, 3D para-FAZ vessel density), vessel density, extrafoveal avascular zones, and neovascularization. Assessing patients with DR using a full-retinal slab OCTA image can limit segmentation errors and confounding factors such as those related to center-involved diabetic macular edema. Given emerging data suggesting the importance of the peripheral retinal vasculature in assessing and predicting DR progression, wide-field OCTA imaging should also be used. Finally, the use of automated methods and algorithms for OCTA image analysis, such as those that can distinguish between areas of true and false signals, reconstruct images, and produce quantitative metrics, such as FAZ area, will greatly improve the efficiency and standardization of results between studies. Most importantly, clinical trial protocols should account for the relatively high frequency of poor-quality data related to sub-optimal imaging conditions in DR and should incorporate time for assessing OCTA image quality and re-imaging patients where necessary.
Reply to: Correspondence on “Hepatopulmonary syndrome is associated with low sphingosine-1-phosphate levels and can be ameliorated by the functional agonist fingolimod”
Authors: Sukriti Baweja, Chhagan Bihari, Anupama Kumari, Dinesh Mani Tripathi, Shiv Kumar Sarin
Journal: Journal of Hepatology (2023)
Pathologic Lymph Node Regression After Neoadjuvant Chemotherapy Predicts Recurrence and Survival in Esophageal Adenocarcinoma: A Multicenter Study in the United Kingdom
Authors: Jonathan L. Moore, Michael Green, Aida Santaolalla, Harriet Deere, Richard P.T. Evans, Mona Elshafie, Anita Lavery, Damian T. McManus, Andrew McGuigan, Rosalie Douglas, Joanne Horne, Robert Walker, Hira Mir, Monica Terlizzo, Sivesh K. Kamarajah, Mieke Van Hemelrijck, Nick Maisey, Ailsa Sita-Lumsden, Sarah Ngan, Mark Kelly, Cara R. Baker, Sacheen Kumar, Jesper Lagergren, William H. Allum, James A. Gossage, Ewen A. Griffiths, Heike I. Grabsch, Richard C. Turkington, Tim J. Underwood, Elizabeth C. Smyth, Rebecca C. Fitzgerald, David Cunningham, Andrew R. Davies, S. Puig, A. Chaudry, A. Jacques, N. Griffin, V. Goh, K. Owczarczyk, A Qureshi, M. Subesinghe, F. Chang, U. Mahadeva, B. Gill-Barman, S. George, M. Ong, J. Waters, M. Cominos, T. Sevitt, M. Hill, O. Hynes, G. Tham, W R C Knight, J. M. Dunn, S. S. Zeki
Journal: Journal of Clinical Oncology (2023)

PURPOSE There is limited evidence regarding the prognostic effects of pathologic lymph node (LN) regression after neoadjuvant chemotherapy for esophageal adenocarcinoma, and a definition of LN response is lacking. This study aimed to evaluate how LN regression influences survival after surgery for esophageal adenocarcinoma. METHODS Multicenter cohort study of patients with esophageal adenocarcinoma treated with neoadjuvant chemotherapy followed by surgical resection at five high-volume centers in the United Kingdom. LNs retrieved at esophagectomy were examined for chemotherapy response and given a LN regression score (LNRS)—LNRS 1, complete response; 2, &lt;10% residual tumor; 3, 10%-50% residual tumor; 4, &gt;50% residual tumor; and 5, no response. Survival analysis was performed using Cox regression adjusting for confounders including primary tumor regression. The discriminatory ability of different LN response classifications to predict survival was evaluated using Akaike information criterion and Harrell C-index. RESULTS In total, 17,930 LNs from 763 patients were examined. LN response classified as complete LN response (LNRS 1 ≥1 LN, no residual tumor in any LN; n = 62, 8.1%), partial LN response (LNRS 1-3 ≥1 LN, residual tumor ≥1 LN; n = 155, 20.3%), poor/no LN response (LNRS 4-5; n = 303, 39.7%), or LN negative (no tumor/regression; n = 243, 31.8%) demonstrated superior discriminatory ability. Mortality was reduced in patients with complete LN response (hazard ratio [HR], 0.35; 95% CI, 0.22 to 0.56), partial LN response (HR, 0.72; 95% CI, 0.57 to 0.93) or negative LNs (HR, 0.32; 95% CI, 0.25 to 0.42) compared with those with poor/no LN response. Primary tumor regression and LN regression were discordant in 165 patients (21.9%). CONCLUSION Pathologic LN regression after neoadjuvant chemotherapy was a strong prognostic factor and provides important information beyond pathologic TNM staging and primary tumor regression grading. LN regression should be included as standard in the pathologic reporting of esophagectomy specimens.
Rational design of oral drugs targeting mucosa delivery with gut organoid platforms
Authors: Tianjian Tong, Yijun Qi, Derrick Rollins, Luke D. Bussiere, Debarpan Dhar, Cathy L. Miller, Chenxu Yu, Qun Wang
Journal: Bioactive Materials (2023)

Effective oral drugs and vaccines require high delivery efficiency across the gastrointestinal epithelia and protection of medically effective payloads (i.e., immunogens) against gastric damage. In this study, hollowed nanocarriers (NCs: silica nanospheres and gold nanocages) with poly-l-lysine (PLL) coating and mammalian orthoreovirus cell attachment protein σ1 functionalization (NC-PLL-σ1) were explored as functional oral drug delivery vehicles (ODDVs). The transport of these ODDVs to mucosal lymphoid tissues could be facilitated by microfold cells (M-cells) mediated transcytosis (via σ1-α2-3-linked sialic acids adherence) across gastrointestinal epithelia. PLL coating provided protection and slow-release of rhodamine 6 G (R6G), a model payload. The transport effectiveness of these ODDVs was tested on intestinal organoid monolayers in vitro. When compared with other experimental groups, the fully functionalized ODDV system (with PLL-σ1) demonstrated two significant advantages: a significantly higher transport efficiency (198% over blank control at 48 h); and protection of payloads which led to both better transport efficiency and extended-release of payloads (61% over uncoated carriers at 48 h). In addition, it was shown that the M cell presence in intestinal organoid monolayers (modulated by Rank L stimulation) was a determining factor on the transport efficiency of the ODDVs: more M-cells (induced by higher Rank L) in the organoid monolayers led to higher transport efficiency for ODDV-delivered model payload (R6G). The fully functionalized ODDVs showed great potential as effective oral delivery vehicles for drugs and vaccines.
Measles virus transmission patterns and public health responses during Operation Allies Welcome: a descriptive epidemiological study
Authors: Nina B Masters, Andrew S Beck, Adria D Mathis, Jessica Leung, Kelley Raines, Prabasaj Paul, Scott E Stanley, Alden L Weg, Emily G Pieracci, Shannon Gearhart, Madina Jumabaeva, Bettina Bankamp, Paul A Rota, David E Sugerman, Paul A Gastañaduy
Journal: The Lancet Public Health (2023)

On Aug 29, 2021, Operation Allies Welcome (OAW) was established to support the resettlement of more than 80 000 Afghan evacuees in the USA. After identification of measles among evacuees, incoming evacuee flights were temporarily paused, and mass measles vaccination of evacuees aged 6 months or older was introduced domestically and overseas, with a 21-day quarantine period after vaccination. We aimed to evaluate patterns of measles virus transmission during this outbreak and the impact of control measures.
Creating and Transferring an Innervated, Vascularized Muscle Flap Made from an Elastic, Cellularized Tissue Construct Developed In Situ
Authors: Hideyoshi Sato, Keishi Kohyama, Takafumi Uchibori, Keisuke Takanari, Johnny Huard, Stephen F. Badylak, Antonio D'Amore, William R. Wagner
Journal: Advanced Healthcare Materials (2023)

Reanimating facial structures following paralysis and muscle loss is a surgical objective that would benefit from improved options for harvesting appropriately sized muscle flaps. The objective of this study is to apply electrohydrodynamic processing to generate a cellularized, elastic, biocomposite scaffold that could develop and mature as muscle in a prepared donor site in vivo, and then be transferred as a thin muscle flap with a vascular and neural pedicle. First, an effective extracellular matrix (ECM) gel type is selected for the biocomposite scaffold from three types of ECM combined with poly(ester urethane)urea microfibers and evaluated in rat abdominal wall defects. Next, two types of precursor cells (muscle-derived and adipose-derived) are compared in constructs placed in rat hind limb defects for muscle regeneration capacity. Finally, with a construct made from dermal ECM and muscle-derived stem cells, protoflaps are implanted in one hindlimb for development and then microsurgically transferred as a free flap to the contralateral limb where stimulated muscle function is confirmed. This construct generation and in vivo incubation procedure may allow the generation of small-scale muscle flaps appropriate for transfer to the face, offering a new strategy for facial reanimation.
Flashback Foreword: Radical Cystectomy in the Treatment of Bladder Cancer
Authors: George J. Bosl
Journal: Journal of Clinical Oncology (2023)

Article Tools FLASHBACK FOREWORD Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES JCO Flashback: Long-Term Outcomes of Radical Cystectomy in Patients With Invasive Bladder Cancer (2001). July 27, 2023 Radical Cystectomy in the Treatment of Invasive Bladder Cancer: Long-Term Results in 1,054 Patients. July 27, 2023 ARTICLE CITATION DOI: 10.1200/JCO.23.00634 Journal of Clinical Oncology - published online before print July 27, 2023 PMID: 37499355 Flashback Foreword: Radical Cystectomy in the Treatment of Bladder Cancer George J. Bosl , MD, FASCO, MACP1,2,3xGeorge J. BoslSearch for articles by this author Show More 1Associate Editor, Journal of Clinical Oncology, Alexandria, VA2Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY3Weill Cornell Medical College, New York, NY https://doi.org/10.1200/JCO.23.00634 First Page Full Text PDF Figures and Tables © 2023 by American Society of Clinical OncologyTHE TAKEAWAYIn the companion to this article, Stein et al1 reported excellent 5- and 10-year recurrence-free survival and a low postoperative mortality in patients with advanced urothelial carcinoma (UC) of the bladder treated by radical cystectomy and pelvic iliac lymph node dissection. This study serves as the gold standard reference for surgical studies of locally advanced bladder UC that investigate new surgical methods (eg, robotic surgery), optimal node template, and quality outcomes. The study's results also showed the increasing likelihood of distant metastasis and worse survival with higher P stage and positive lymph node disease, highlighting the need for effective (neo)adjuvant chemotherapy to achieve optimal disease control after diagnosis.AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTFlashback Foreword: Radical Cystectomy in the Treatment of Bladder CancerThe following represents disclosure information provided by the author of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).No potential conflicts of interest were reported. Companion JCO Flashback: Long-Term Outcomes of Radical Cystectomy in Patients With Invasive Bladder Cancer (2001) Radical Cystectomy in the Treatment of Invasive Bladder Cancer: Long-Term Results in 1,054 Patients